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. 2017 Jul 3;114(29):E5920–E5929. doi: 10.1073/pnas.1701832114

Fig. 6.

Fig. 6.

Targeted gene therapy reduces microglial activation in Ppt1−/− mice. (A) Representative images of CD68 staining in treated animals and controls at 7 mo. CD68 staining was examined in the primary motor cortex, VPM/VPL of the thalamus, and ventral horn of the lumbar spinal cord showing differential patterns of reduction of microglial activation in intracranially (IC-AAV2/9), intrathecally (IT-AAV2/9), and combination intracranially and intrathecally (IC/IT-AAV2/9) treated mice, compared with untreated Ppt1−/− and wild-type control mice. IC/IT-AAV2/9 mice showed an overall greater reduction in microglial activation than either IC-AAV2/9 or IT-AAV2/9 therapy alone. The dotted lines demarcate the boundary between the gray and white matter in spinal cord sections. [Scale bars, 200 μm and 25 μm (Insets).] (Insets) Selected from corresponding lower-power views. (B) Thresholding image analysis at 3-, 5-, and 7-mo time points revealed a significant but region-specific pattern in the impact upon microglial activation based on the site of vector administration, with IC/IT-AAV2/9–treated mice showing the greatest overall reduction of microglial activation. Significance is compared with untreated Ppt1−/− mice. Dots represent scatterplots of individual animals. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA with post hoc Bonferroni correction. Values shown are mean ± SEM (n = 3 mice per group).